Outline

Background: Even retarded dihydropyridine (DHP) calcium antagonists for antihypertensive therapy may activate the sympathetic nervous system (SNS), while non-DHP calcium antagonists may reduce SNS activity. Angiotensin-converting-enzyme (ACE) inhibitors are thought to have no or inhibitory effects on sympathetic tone. Trandolapril/verapamil sustained release (SR) (Tarka) is an oral fixed-dose combination of the ACE inhibitor trandolapril and the SR formulation of the phenylalkylamine calcium antagonist verapamil. We compared the effects of trandolapril/verapamil on SNS activity to those of a fixed-dose combination of the ACE inhibitor ramipril and the retarded DHP calcium antagonist felodipine (Delmuno). We hypothesized that trandolapril/verapamil would reduce SNS activity.

Methods: 34 hypertensive patients were included in a double blind, randomised study and, following a two-week placebo run in, were treated with trandolapril/verapamil 2/180 mg or ramipril/felodipine 5/5mg. Plasma noradrenaline (NA) was measured at baseline and after 8 weeks of treatment. Blood pressure (BP) and heart rate (HR) were secondary parameters. Data were analyzed with t-test or Mann-Whitney test (meanÂ±SD).

Results: Baseline plasma NA concentrations were similar in both treatment arms (P= 0.52). After 8 weeks of treatment, plasma NA was reduced in the trandolapril/verapamil group (-57Â±146 pg/ml) but was increased in the ramipril/felodipine group (+136Â±192 pg/ml, P= 0.002 vs. trandolapril/verapamil). BP increased in all patients during the placebo run-in but was lowered to a similar degree by both combinations (delta systolic BP trandolapril/verapamil vs. ramipril/felodipine: -5Â±18 vs. -15Â±13 mmHg, P= 0.10; delta diastolic BP trandolapril/verapamil vs. ramipril/felodipine: -10Â±10 vs. -5Â±9 mmHg, P= 0.18). HR remained unchanged by either treatment.